Ovarian cancer is the fifth leading cause of cancer-related deaths in women and causes more deaths than all other gynecologic malignancies combined. This poor prognosis is due to in part to the absence of early clinical symptoms and the lack of biomarkers for early detection. Discovering an effective means for the diagnosis and/or early detection of ovarian cancer is an intensely sought goal. The proposed long term objective is to define a method for the diagnosis of early stage ovarian carcinoma. A comprehensive analysis of gene promoter-associated CpGislands that are aberrantly methylated during oncogenic transformation will be performed. Utilizing our extensive clinical and laboratory resources, the potential use o a serum-based assay to detect aberrantly methylated genomic DNA will be investigated in translational research aimed at early detection and diagnosis of ovarian cancer. Specific Aim 1: Identify gene promoter-associated CpG islands that are differentially methylated in ovarian carcinomas by representational difference analysis (RDA) of methylated CpG islands that were PCR- amplified from ovarian epithelial tumor DNA. Specific Aim 2: Define a subset of ovarian tumor-specific aberrantly methylated genes that can be used in a serum-based assay for ovarian cancer detection. The experiments outlined in this proposal take a novel approach for defining biomarkers for ovarian cancer and may potentially form the basis for an effective ovarian cancer diagnostic assay likely to have significant impact on ovarian cancer survival.